Granulomatous inflammation represents a complex and tightly regulated response to multiple types of antigens. Cell-antigen, as well as cell-cell, interactions determine the fate of the granulomatous response: involution or tissue destruction. Although Fas ligand (FasL)-mediated apoptosis, or programmed cell death, has previously been shown important in both human and animal inflammation, its potential role in regulating granuloma development is yet to be defined. Using a murine model of pulmonary granuloma formation, we have demonstrated that FasL is expressed and apoptosis is active in lung granuloma. Preliminary data also suggest that FasL-deficient animals develop an aberrant granulomatous response. We hypothesize that Fas and FasL-mediated signals are essential to the resolution of the pulmonary granulomatous response. Using standard techniques and a well-characterized model of Schistosoma (S.) mansoni egg-induced synchronous lung granulomas, we propose to first characterize the expression of Fas and FasL and the degree of apoptosis during granuloma development. Second, using FasL-deficient (gld) mice, we will determine the impact of defective Fas/FasL signaling on granuloma formation, cytokine production and resolution. As a result, we will show that the Fas/FasL signaling pathway plays an integral role in down-modulating the granulomatous inflammatory process.